Abstract

Here we report that the recently identified DNA modification N6-methyl-2-deoxyadenosine (m6dA) is dynamically regulated in post-mitotic neurons and accumulates within promoters and genomic coding sequences of neurons activated by fear extinction learning in adult C57/Bl6 mice. The deposition of m6dA leads to an open chromatin state as well as the recruitment of the activating transcription factor Yin-Yang 1 and RNA polymerase II, which are critical for activity-induced brain-derived neurotrophic factor gene expression and required for the formation of fear extinction memory. These findings expand the scope of DNA modifications in the adult brain and highlight the discovery of DNA m6dA as a novel neuroepigenetic mechanism associated with learning and memory.

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